Image-Based Modeling of Drug Delivery during Intraperitoneal Chemotherapy in a Heterogeneous Tumor Nodule

Area of Science:

• Biomedical Engineering
• Mathematical Oncology
• Pharmacokinetics

Background:

• Intraperitoneal (IP) chemotherapy is vital for peritoneal carcinomatosis but faces challenges with drug penetration into tumors.
• Tumor pathophysiology and heterogeneous vasculature complicate drug delivery efficacy.
• Experimental studies are limited; mathematical modeling offers a cost-effective and efficient alternative for investigation.

Purpose of the Study:

• To develop and utilize a numerical model for investigating drug delivery during IP chemotherapy.
• To incorporate tumor heterogeneity, including vasculature, drug binding, and cellular uptake, into the model.
• To analyze the impact of tumor vascular networks on drug distribution and treatment outcomes.

Main Methods:

• Developed a numerical model using image processing to reconstruct tumor geometry from actual patient scans.
• Incorporated parameters such as drug binding and cancer cell uptake.
• Simulated 60 minutes of Doxorubicin IP treatment to assess drug concentration, penetration, and cell viability.

Main Results:

• The model predicted an Area Under the Curve (AUC) of 295.18 mol·m⁻³·s⁻¹ for free drug concentration.
• Drug penetration, indicated by half-width (W₁/₂), ranged from 0.11 to 0.14 mm.
• A fraction of 20.4% of cancer cells were predicted to be killed by the end of the simulated treatment.
• Heterogeneous tumor vasculature significantly influenced interstitial fluid velocity, pressure, and drug concentration distribution.

Conclusions:

• Tumor vascular heterogeneity is a critical factor influencing drug delivery in IP chemotherapy.
• The developed numerical model provides valuable insights into drug penetration and efficacy.
• This methodology shows potential for personalized treatment planning in patient-specific studies for peritoneal carcinomatosis.